Low levels of contaminating malignant cells are present in autologous bone marrow (Simpson S. J., et al. Blood 23:1062 (1995)) of cancer patients and mobilized peripheral blood stem cell grafts (Brugger W., et al. Blood 83:636 (1994)). In some cases residual malignant cells have led to a relapse in the transplanted patients (Rill, D. R., et al. Blood 84:380 (1994)). Several techniques have been used to prevent relapse due to co-transplantation of the malignant cells by selectively removing the malignant cells from the grafts.
In one approach, CD34-coupled immunomagnetic beads have been used to selectively isolate the hematopoietic progenitor cells from bone marrow containing malignant cells (Berenson, R. J., et al. Blood 77:1717 (1991); De Wynter, E. A., et al. Stem Cells 13:524 (1995)). Unfortunately, this procedure can only be used to remove hematopoietic progenitor cells from bone marrow containing malignant cells that do not express the CD34 antigen, since the CD34 antigen has been reported to be expressed on 9 out of 63 breast cancer, 2 out of 11 squamous cell sarcomas of the lung and 3 out of 12 small cell lung cancers (Kohler G, et al. Blood 86:497a (1995) (abstract)).
In another approach, the action of either an antibody and its complement (Slaper-Cortenbach, I. C. M., et al. Exp Hematol. 18:49 (1990)), cytotoxic drugs (Uckun, F. M., et al. Blood 69:361 (1987)), or a photosensitizer (Levy, J. G., et al. Stem Cells 13:336 (1995)) has been used to selectively kill the malignant cells. The photoinactivation of malignant cells has been successfully achieved using a variety of photosensitizers such as merocyanine-540 (MC 540) (Atzpodien, J., et al. Cancer Res. 46:4892 (1986); Sieber, F. Photochem Photobiol. 46:71 (1987)), dihematoporphyrin ether (DHE) (Atzpodien, J., et al. Blood 70:484 (1987)), pyrene-containing sensitizers (P12) (Fibach, E., et al. Exp Hematol. 18:89 (1990); Fibach, E., et al. Leukemia Res. 16:453 (1992)), and sulphonate aluminum phthalocyanine (AlSPc) (Singer, C. R. J., et al. Br. J. Haematol. 68:417 (1988)).
The relatively low cytotoxicity of the phthalocyanines (Pc) and their resistance to chemical and photochemical degradation (Chan, W. S., et al. Br. J. Cancer 53:255 (1986)) led to the development of new Pc photosensitizers (Oleinick, N. L., et al. Photochem. Photobiol. 57:242 (1993)). One of these is hydroxysiloxy-dimethylpropyl-N-dimethyl silicon phthalocyanine (HOSiPcOSi(CH.sub.3).sub.2 (CH.sub.2).sub.3 N(CH.sub.3).sub.2) ("Pc 4") (Oleinick, N. L., supra; Zaidi, S. I. A., et al. Photochem. Photobiol. 58:204 (1993)), which has been shown to effectively photoinactivate viruses (Ben-Hur, E., et al. Photochem. Photobiol. 62:575 (1995)), and parasites (Ben-Hur, E., et al.: Photodynamic decontamination of blood for transfusion, in Brault D, G Jori G, Ehrenberg B (eds): Photodynamic therapy of cancer II, SPIE, vol. 2325, p. 166 (1995); Gottlieb, P., et al. Photochem. Photobiol. 62:869 (1996)) in blood products, and mammalian cells such as V79 (a chinese hamster lung fibroblast cell line) (Zaidi, S. I. A., et al., supra).